EP2581107A1 - Detection/stimulation microprobe implantable in venous, arterial or lymphatic networks - Google Patents

Abstract

The microprobe has a microcable (40) comprising a core cable (11) that includes a composite structure formed from a structuring material and a radio-opaque material constituting approximately 0.008 mm square of a section of the core cable in a proportion equal to 50 percent. A stripped zone (30) is formed in an insulation layer (20) so as to form an electrode having a cumulative total surface area equal to 20 mm square. A reducing unit is used for gradually reducing rigidity along the microprobe between proximal end portion and distal end portion.

Description

The invention relates generally to "active implantable medical devices" as defined by Council Directive 90/385 / EEC of 20 June 1990.

This definition includes, in particular, cardiac implants responsible for monitoring cardiac activity and generating pacing, defibrillation and / or resynchronization pulses in the event of a rhythm disorder detected by the device. It also includes neurological devices, cochlear implants, diffusion pumps for medical substances, implanted biological sensors, etc.

These devices comprise a housing generally designated "generator", electrically and mechanically connected to one or more intracorporeal "probes" provided with (s) electrodes intended to come into contact with the tissues on which it is desired to apply stimulation pulses and / or collect an electrical signal: myocardium, nerve, muscle, ...

The present invention more specifically relates to a microprobe of detection / stimulation intended to be implanted in venous, arterial or lymphatic networks.

• facilité d'implantation par le médecin dans un réseau de vaisseaux du patient, et en particulier facilité : à faire progresser la sonde dans les vaisseaux par poussée, à faire suivre à la sonde des trajets tortueux et passer des embranchements, et à transmettre des couples ;
• visibilité aux rayons X afin de permettre au médecin une navigation aisée à travers les vaisseaux du réseau sous radioscopie X ;
• atraumaticité de la sonde au niveau des veines, ce qui nécessite une grande souplesse de structure et l'absence de transition rigide ou d'angle vif ;
• aptitude à transmettre un signal électrique aux tissus et à faire des mesures électriques monopolaires ou multipolaires de manière stable ;
• biocompatibilité avec les tissus vivants pour une implantation à long terme ;
• capacité à se connecter à un appareil implantable source de transmission du signal ;
• aptitude à la stérilisation (rayons gamma, température ...) sans subir de dommages;
• biostabilité, en particulier résistance à la corrosion dans le milieu vivant et résistance à la sollicitation mécanique en fatigue liée aux mouvements du patient et des organes ;
• compatibilité avec l'imagerie IRM, particulièrement importante en neurologie.

The current principle of electrical stimulation of tissues is based on a device, generally called "probe", which is an object implanted through various vessels, venous, arterial or lymphatic in particular, and whose function is to transmit an electrical signal to the tissue -cible while guaranteeing the following properties:

• ease of implantation by the physician in a network of vessels of the patient, and in particular facilitated: to advance the probe in the vessels by pushing, to follow the probe tortuous paths and pass branch lines, and to transmit couples ;
• X-ray visibility to allow the physician easy navigation through the X-ray network vessels;
• atraumaticity of the probe at the level of the veins, which requires a great flexibility of structure and the absence of rigid transition or sharp angle;
• ability to transmit an electrical signal to tissues and to make monopolar or multipolar electrical measurements in a stable manner;
• biocompatibility with living tissue for long-term implantation;
• ability to connect to an implantable device that is a source of signal transmission;
• ability to sterilize (gamma rays, temperature ...) without being damaged;
• biostability, in particular resistance to corrosion in the living medium and resistance to mechanical stress in fatigue related to the movements of the patient and organs;
• compatibility with MRI imaging, particularly important in neurology.

The current architecture of the probes meeting these needs can be summarized as a generally hollow structure to allow the passage of a mandrel or a guide wire, and comprising insulated conductor cable components connected to mechanical electrodes for ensure electrical conductivity, radio-opacity ...

It is therefore probes requiring a complex assembly of a large number of parts, son and associated insulators, creating significant risk of rupture given the long-term mechanical stresses to which they are exposed.

Examples of such probes are given in the US 6,192,280 A and US 7,047,082A , or in the US 5,246,014A ..

Among the difficulties encountered, mention may be made of the management of stiffness gradients related to the mechanical parts used, which strongly affect the implantability and mechanical resistance properties over the long term (fatigue).

In addition, in order to seal the internal lumen of the probes, the entry of blood degrading the performance at laying and long-term, valves and other complex devices with significant associated risks are used.

Other difficulties can also arise in terms of assembly fatigue. Indeed, any stiffness transition zone is likely to induce risks of fatigue, difficulties to sterilize due to the presence of difficult access areas, and problems with conducting conductor junctions at the connection with the electrodes and the connector.

In addition, the clinical trend in the field of implantable probes is to reduce their size to make them less invasive and easier to handle through the vessels.

The current size of the implantable probes is typically in the range of 4 to 6 French (1.33 to 2 mm) in their active part, ie the most distal part carrying the electrode or electrodes - even if the probe body, in the less distal part, uses smaller diameter conductors, as for example in the US 5,246,014A above, which, at the probe body, certainly includes a conductor whose diameter does not exceed 1 French (0.33 mm), but whose overall diameter of the distal active portion, at the location of the screw anchorage, is of several French.

However, it is clear that reducing the size of the probes would increase their complexity and impose technical constraints that generate risks.

However, such a reduction, to less than 2 French (0.66 mm) for example, would open perspectives of medical applications in various fields ranging from cardiology to neurology in the presence of a venous, arterial or even lymphatic network. , such as the cerebral venous network or the venous network of the coronary sinus.

Today, electrical stimulation technology has led to significant advances in the field of neuromodulation, which involves stimulating target areas of the brain for the treatment of Parkinson's disease, epilepsy and other neurological diseases.

One could thus imagine with this type of technology to treat new regions difficult to reach today, this by means of small stimulation probes, or "microworlds", with a great robustness in order to guarantee the long-term biostability. Such a technique would allow a less invasive approach to these treatments and above all a superior efficacy of the treatments administered.

It would be possible to connect one or more microwaves across the relevant vessel network to their target location. Their implementation could be carried out, because of their reduced size, by guiding devices used today in interventional neuroradiology for the release of springs ( coils ) during the treatment of intracranial aneurysms.

Also, the object of the present invention is to provide such a small "microprobe" which would be in accordance with the general properties of the implantable probes as enumerated above, while reducing its complexity and, therefore, done, the final cost.

The size of this microprobe should in particular make it possible to reach venules of very small dimensions, inaccessible today with devices of greater size. The microprobe of the invention should also facilitate substantially navigability in the venous, arterial or lymphatic networks because of its flexibility, amplified by its small size.

According to the invention, this object is achieved by means of a probe of a general type comprising, as disclosed by the US 5,246,014A mentioned above, a microcable having a diameter of not more than 2 French (0.66 mm), this microcable comprising: an electrically conductive core cable of diameter at most equal to 0.50 mm, formed by a strand of a plurality of strands of unit diameter at most equal to 40 microns, the core cable comprising a structuring material, in particular a stainless steel, cobalt alloy, precious metal, titanium or NiTi alloy, having a high resistance to fatigue; and a polymer insulation layer partially surrounding the core cable to a thickness of at most 30% of the core cable diameter.

In a characteristic manner of the invention, this probe is a microprobe consisting in its active portion, distal, by said microcable with a diameter of at most 2 French (0.66 mm).

For this purpose, the core cable of the microcable has a composite structure formed from, at least, said structuring material and a radiopaque material constituting at least about 0.008 mm ² of the section of the core cable in a proportion to plus 50%. In addition, at least one stripped zone is formed in the insulation layer so as to form at least one electrode on a cumulative total surface area at most equal to 20 mm ² . Finally, stiffness degressivity means are provided along the microprobe between its proximal portion and its distal portion.

The microprobe may be rectilinear or, preferably, shaped at the level of the electrodes according to at least one electrical contact and mechanical stabilization preform

Thus, it is understood that with a diameter of not more than 0.50 mm, the core cable constituting the microcable of the microprobe according to the invention has great flexibility, favorable to its handling by the doctor, especially during its implantation for example when it involves introducing it into networks of vessels with strong tortuosities and numerous branches and to avoid traumas that could lead to much more rigid probes, incompatible with the tissues.

On the other hand, the choice of a stranded multifilament structure composed of very fine strands, with a unit diameter of at most 40 μm, preferably between 20 and 40 μm, makes it possible to increase the resistance to mechanical fatigue of the cable. of heart due to the movements of the patient and organs, knowing that the limit of bending rupture of a wire is substantially inversely proportional to its diameter. In order to reinforce this important property of biostability, it is advantageous for the strands themselves to be made of a structuring material whose intrinsic fatigue resistance is high, such as for example the materials mentioned above. that is to say, stainless steels, cobalt alloys, titanium and NiTi alloy known in particular under the name of nitinol. To these metals responsible for ensuring the mechanical properties of the heart cable is added a radiopaque material intended to make the microprobe visible to X-rays when it is put in place by the doctor. The radiopaque material may be selected from tantalum (Ta), tungsten (W), iridium (Ir), platinum (Pt), gold (Au) and their alloys.

Concretely, the invention provides that the composite structure thus obtained of the core cable can be made by composite strands consisting, at least, of a structuring material and a radiopaque material, or by strands consisting of structuring material and strands made of radiopaque material. The plurality of strands of the strand advantageously comprises between 15 and 300 strands.

In order to make electrical contact with the tissues and to transmit the electrical signal, the invention proposes a solution which consists in using the heart cable itself to form the electrodes of the microprobe by providing bare areas in an insulation layer surrounding the cable. The invention recommends that the insulation layer, preferably made of fluoropolymer, does not exceed in thickness 30% of the diameter of the core cable, this in order to avoid the effect of staircase at the edge of the electrodes which could impair electrical contact with tissue. Finally, the means of degressivity of rigidity (that is to say, which provide a decreasing stiffness from the proximal portion to the distal portion) provided by the invention facilitate the implantation of the microprobe thanks to the faculty that is given to be pushed inside the vessels. As will be seen in detail below, the means of decreasing stiffness can be achieved, in accordance with the invention, by a staged stack of tubes nested within each other, or by a succession of isodiameter tubes of increasing rigidity.

The microprobe, once in place, is stabilized in position by preforming, S or three-dimensional spiral, which also ensures permanent electrical contact of the electrodes with the tissues. Advantageously, the microprobe also comprises local reinforcement means.

In order to limit the heating of the core rope by skin effect in an MRI imaging, the invention recommends that the strands comprise an outer layer of low magnetic susceptibility material, less than 2 .m ³ 000.10 ^-12. mole ^-1 .

The material with low magnetic susceptibility can be, alternatively, tantalum (Ta), titanium (Ti), rhodium (Rh), molybdenum (Mo), tungsten (W), palladium (Pd), gold (Au) and their alloys.

• Les Figures 1a à 1d sont des vues en coupe de brins constitués d'un matériau structurant et d'un matériau radio-opaque.
• Les Figures 2a à 2f sont des vues en coupe de câbles de coeur formés de brins montrés sur les Figures 1a à 1d.
• La Figure 3 est une vue en coupe d'un câble de coeur formé de brins structurants et de brins radio-opaques.
• Les Figures 4a à 4d sont des vues de côté de préformes de microsondes selon l'invention.
• La Figure 5 est une vue en perspective d'un microcâble présentant une zone totalement dénudée de la couche d'isolement.
• La Figure 6 est une vue en perspective d'un microcâble présentant une zone partiellement dénudée de la couche d'isolement.
• Les Figures 7a et 7b sont des vues en coupe de microcâbles présentant des zones de couche d'isolement partiellement dénudées.
• La Figure 8 est une vue de côté en coupe d'une microsonde présentant un empilement de tubes de gradient de rigidité.
• La Figure 9 est une vue en perspective d'une microsonde munie d'un dispositif de renforcement local.
• La Figure 10a est une vue de côté d'un premier mode de réalisation d'une microsonde conforme à l'invention.
• La Figure 10b est une vue en coupe de la section distale de la microsonde de la Figure 10a.
• La Figure 10c est une vue en coupe d'un brin unitaire du câble de coeur de la microsonde de la Figure 10b.
• La Figure 10d est une vue en perspective de la microsonde de la Figure 10a munie d'un connecteur IS-1.
• La Figure 10e est une vue en perspective montrant une implantation de la microsonde de la Figure 10a dans les veines coronaires.
• La Figure 11a est une vue en coupe d'un deuxième mode de réalisation d'une microsonde conforme à l'invention.
• La Figure 11b est une vue en coupe d'un brin unitaire du câble de coeur de la microsonde de la Figure 11a.
• Les Figures 11c et 11d sont des vues en perspective montrant des implantations de la microsonde de la Figure 11a dans une cavité du coeur.
• La Figure 12a est une vue en coupe d'un troisième mode de réalisation d'une microsonde conforme à l'invention.
• La Figure 12b est une vue en coupe d'un brin unitaire du câble de coeur de la microsonde de la Figure 12a.
• La Figure 12c est une vue en coupe d'un exemple d'implantation de la microsonde de la Figure 12a dans les tissus cérébraux.

An embodiment of the device of the invention will now be described with reference to the appended drawings in which the same reference numerals designate identical or functionally similar elements from one figure to another.

• The Figures 1a to 1d are sectional views of strands consisting of a structuring material and a radiopaque material.
• The Figures 2a to 2f are cross-sectional views of heart cables formed of strands shown on the Figures 1a to 1d .
• The Figure 3 is a sectional view of a core cable formed of structural strands and radiopaque strands.
• The Figures 4a to 4d are side views of microsonde preforms according to the invention.
• The Figure 5 is a perspective view of a microcable having a completely stripped area of the insulation layer.
• The Figure 6 is a perspective view of a microcable having a partially stripped area of the insulation layer.
• The Figures 7a and 7b are sectional views of microcables with partially exposed isolation layer areas.
• The Figure 8 is a sectional side view of a microprobe with a stack of stiffness gradient tubes.
• The Figure 9 is a perspective view of a microprobe with a local reinforcement device.
• The Figure 10a is a side view of a first embodiment of a microprobe according to the invention.
• The Figure 10b is a sectional view of the distal section of the microprobe of the Figure 10a .
• The Figure 10c is a sectional view of a unitary strand of the core cable of the microprobe of the Figure 10b .
• The Figure 10d is a perspective view of the microprobe of the Figure 10a equipped with an IS-1 connector.
• The Figure 10e is a perspective view showing an implantation of the microprobe of the Figure 10a in the coronary veins.
• The Figure 11a is a sectional view of a second embodiment of a microprobe according to the invention.
• The Figure 11b is a sectional view of a unitary strand of the core cable of the microprobe of the Figure 11a .
• The Figures 11c and 11d are perspective views showing implantations of the microprobe of the Figure 11a in a cavity of the heart.
• The Figure 12a is a sectional view of a third embodiment of a microprobe according to the invention.
• The Figure 12b is a sectional view of a unitary strand of the core cable of the microprobe of the Figure 12a .
• The Figure 12c is a sectional view of an example of implantation of the microprobe of the Figure 12a in the brain tissue.

The probes concerned by the invention are microsondes of stimulation intended to be implanted in venous, arterial or lymphatic networks, and whose diameter does not exceed 2 French (0.66 mm). They are constituted in their active part, distal, by a microcable formed of a conductive core cable partially surrounded by an insulation layer defining at least one stimulation electrode.

The service life is a fundamental parameter which must be absolutely taken into account when designing any medical device, in particular the microsondes of stimulation, objects of the invention. Indeed, the beating of the heart and the movement of the organs induce on this type of devices flexural deformations which must be perfectly controlled.

In general, for a cylindrical wire of diameter d , the bending deformation can be characterized by the ratio ε = d / D where D represents the diameter of the curvature imposed on the wire by the bending stress. This constraint, for example related to the heartbeat, may be experienced by the strand on 400.10 ⁶ cycles over a period of 10 years, causing fatigue of the material may cause its rupture and limit its life.

Thus a microprobe of stimulation by the venous network, for example, can be the seat of deformations of curvature superior to a normal probe insofar as it must follow the deformations of the veins, which causes a greater stress and makes its resistance to fatigue more restrictive.

To increase the fatigue rupture limit of the microworlds, it is therefore advantageous to adopt for the core cable a multiwire structure in the form of a strand of a plurality of conductive strands of small diameter d . The reduction in diameter of the unitary strands makes it possible reduce the stress applied to each of them and therefore increase the fatigue performance of the strand structure. For a given material, it is possible to define a maximum deformation ε _Max corresponding to its fatigue strength limit for a number of deformation cycles equal, for example, to 100 × 10 ⁶ .

The choice of a material constituting the frame of the core cable, which will be called "structuring material", must meet several criteria.

It must in particular be part of materials whose mechanical properties are known for long-term implantable applications and have a maximum deformation ε _Max greater than the deformation that a strand is likely to undergo, while remaining compatible with the technical feasibility and the cost of a strand of very small diameter.

By way of example, for a cobalt alloy of the MP35N type having a maximum deformation ε _Max of 5.10 ^-3 to 100.10 ⁶ cycles and for a diameter of curvature D of 7 mm, the diameter of the unit strand must be less than 35 μm. . A strand of 20 microns will easily resist this stress, while a strand of 40 microns may cause a break before reaching the 100.10 ⁶ cycles. It should be noted that the NiTi alloys exhibit maximum deformation ε _Max greater, from 5 to 9.10 ^-3 , offering even wider possibilities.

In summary, it is proposed by the invention to use as structuring material a stainless steel, a cobalt alloy of the MP35N series, a precious metal, titanium or a NiTi alloy, of high fatigue resistance, to form a multi-filament structure whose strands have a diameter of not more than 40 μm, this dimension allowing on average to guarantee a maximum fatigue rupture strength under the extreme stress conditions to which such structures may be subjected.

Ideally, strands with a diameter of between 20 and 40 μm will be considered, with smaller dimensions that may pose problems of technical feasibility and cost.

In order to guarantee sufficient X-ray visibility for the implantation of the microprobe, it is necessary to introduce a minimum quantity of radio-opaque material along the core cable.

The difficulty in this respect is to reconcile the fatigue resistance of the cable with the radiopacity as well as the resistance to corrosion. Indeed, the most materials used for their X-ray visibility, namely tantalum (Ta), tungsten (W), iridium (Ir), platinum (Pt), gold (Au) and their alloys, do not present not generally a great resistance to fatigue. This is why it is advantageous to adopt in this case a so-called composite cable structure in which a radiopaque material is added to the structuring material within the strand of single strands.

Given the sensitivity of current X-ray equipment, the minimum presence of radiopaque material in the composite structure is estimated to be 0.008 mm ² in the section of the core cable, but the proportion of radiopaque material opaque does not exceed 50%, in order not to degrade the mechanical properties of the strands ensured by the structuring material.

As shown by Figures 1a to 1d , the composite structure of the core cable is made by composite strands consisting, at least, of a structuring material 1 and a radiopaque material 2. More specifically, the Figure 1a represents a strand of which the structuring material 1 is outside the strand and the radiopaque material 2 inside. Conversely, in the strand of the Figure 1b , the structuring material 1 is inside and the radiopaque material 2 outside. The strand of the Figure 1c is made with an alloy 3 of structuring material and radiopaque material. Finally, the strand structure of the Figure 1d is more complex, with two outer and inner sections of radiopaque material 2 surrounding an intermediate section of structuring material 1.

The strands 10 thus obtained can be stranded to form a core cable for the microprobe. On the Figure 2a is shown a strand 11 of nineteen single strands 10. The strand 12 of the Figure 2b is formed by the assembly of seven groups of seven strands 10. The Figure 2c shows a strand 13 of seven groups of 19 strands assembled according to the strand 11 of the Figure 2a . Finally, even more complex structures are illustrated on the Figures 2d to 2f .

According to the variant of the Figure 3 , the core cable 14 has a composite structure made not at the level of the strands but at the level of the cable itself. In the proposed example, strands 10 ₁ made of structuring material surround strands 10 ₂ made of radiopaque material.

As regards the number of strands per strand, it can be calculated that for a diameter of strands of 40 μm and a proportion of radio-opaque material of 50% occupying a section of 0.008 mm ² , the total number of strands of all materials combined is of the order of fifteen strands. Conversely, for a strand diameter of 15 μm and a proportion of radiopaque material of 15% occupying the same section, the total number of strands reaches about 300 strands.

Another important physical feature for a microprobe is its flexibility. It is this property in fact which allows the stimulation device to cross the tortuosities of small radius and to guarantee the absence of traumaticity of the probe by avoiding perforating the veins in which it circulates. To ensure atraumaticity, the end of the microprobe will be rounded half-sphere to minimize this risk of perforation.

Comparing with the existing guidewires used in the same applications, the Applicant has been able to establish that an outer diameter of the core cable at most equal to 0.50 mm provides a sufficient level of flexibility and compatibility. with living tissues. In general, the compatibility of implantable devices with modern medical imaging techniques, such as MRI, is fundamental to ensuring optimal patient care.

Indeed, because of its overall metallic structure, the microprobe has a risk of heating related to currents induced by "skin effect" outside the unit strands under the action of the applied magnetic field. The small diameter given to the strands, however, is favorable to heat dissipation and reduces the heating effects due to MRI. In addition, the thermal energy stored by the materials, already limited in volume, can be further reduced if the unitary strands are coated with an outer layer of low magnetic susceptibility material (the magnetic susceptibility being the faculty of a material to to be magnetized under the action of an external magnetic field).

The most favorable materials in this application are those whose magnetic susceptibility is less than 2 000 × 10 ^-12 m ³ · mol ^-1 , especially tantalum (Ta), titanium (Ti), rhodium (Rh), molybdenum ( Mo), tungsten (W), palladium (Pd), gold (Au) and their alloys.

With regard to the transmission of electrical current to the tissues, the concept retained by the invention is not to provide electrodes, but, as shown in FIG. Figure 5 , using the conductive core cable 11 itself to form the electrodes by partially surrounding the cable with a polymer insulation layer. An electrode 30 is constituted by a stripped zone of cable. This coating technique provides the electrode with sufficient contact to ensure electrical stimulation of the tissue.

The isolation layer 20 covers the entire conductive structure of the core cable 11, except at the electrode zones distributed along the microcable thus produced.

Preferably, the thickness of the insulation layer 20 does not exceed 30% of the outer diameter of the core cable 11, this to avoid the effect of a staircase at the edge of the electrode, the insulation being able to prevent contact of the electrode with the tissue.

• résistance à la fatigue,
• isolement électrique,
• biocompatibilité à long terme,
• biostabilité,
• possibilité de transformation et mise en oeuvre compatible avec le conducteur du câble de coeur.

The characteristics required for the isolation layer 20 are as follows:

• fatigue resistance,
• electrical isolation,
• long-term biocompatibility,
• biostability,
• possibility of transformation and implementation compatible with the conductor of the heart cable.

• les polyuréthannes (PU),
• les polyesters (PET),
• les polyamides (PA),
• les polycarbonates (PC),
• les polyimides,
• les polymères fluorés,
• le polyéther-éther-kétone (PEEK),
• le poly-p-xylylène (parylène),
• le polyméthacrylate de méthyle (PMM).

The materials that can be used in this context are, for example:

• polyurethanes (PU),
• polyesters (PET),
• polyamides (PA),
• polycarbonates (PC),
• polyimides,
• fluorinated polymers,
• polyether ether ketone (PEEK),
• poly-p-xylylene (parylene),
• polymethyl methacrylate (PMM).

• le PTFE (polytétrafluoroéthylène),
• le FEP (propylène perfluoré),
• le PFA (résine de copolymère perfluoroalkoxy),
• le THV (tétrafluoroéthylène, hexafluoropropylène, fluorure de vinylidène),
• le PVDF (polyfluorure de vinylidène),
• l'EFEP (éthylène propylène éthylène fluoré),
• l'ETFE (éthylène tétrafluoroéthylène).

However, preference will be given to materials with high chemical inertness, such as fluoropolymers, which also have a very good quality of insulation. Among these compounds, there may be mentioned:

• PTFE (polytetrafluoroethylene),
• FEP (perfluorinated propylene),
• PFA (perfluoroalkoxy copolymer resin),
• THV (tetrafluoroethylene, hexafluoropropylene, vinylidene fluoride),
• PVDF (polyvinylidene fluoride),
• EFEP (ethylene propylene fluorinated ethylene),
• ETFE (ethylene tetrafluoroethylene).

• co-extrusion sur le conducteur, pour PU, PA, PEEK, polyimides et polymères fluorés ;
• dépôt par trempage dans une solution, pour PU, PA et polyimides ;
• échauffement d'un tube thermorétractable, pour PET et polymères fluorés ;
• dépôt chimique par voie gazeuse, pour le parylène ;
• traitements plasma pour améliorer l'adhésion entre les couches.

The methods for producing the insulation layer on the core cable are multiple depending on the materials used:

• co-extrusion on the conductor, for PU, PA, PEEK, polyimides and fluoropolymers;
• dip deposit in a solution, for PU, PA and polyimides;
• heating of a heat-shrinkable tube, for PET and fluoropolymers;
• chemical deposition by gaseous route for parylene;
• plasma treatments to improve adhesion between layers.

In carrying out these methods, the electrode zones can be defined by depositing isolation layers separated from each other, or by partial stripping of an insulation layer deposited on the entire cable. This stripping is performed for example by laser ablation. As indicated by Figures 6 and 7a, 7b this technique allows partial openings to be made. In particular, Figures 7a and 7b show a microcable with respectively two denuded areas 30 ₁ , 30 ₂ , and five stripped areas 30 ₁ , 30 ₂ , 30 ₃ , 30 ₄ , 30 ₅ .

Advantageously, the electrode zones distributed along the microcable have a cumulative area not exceeding 20 mm ² , for example in the form of 40 electrodes of 0.5 mm ² or 20 electrodes of 1 mm ² , this surface depending on the application as well as electrical performance of the associated equipment.

Ideally, in order to limit current consumption, it is however preferable to produce electrodes with a surface area at most equal to 0.5 mm ² , thus increasing the local current density.

If this proves necessary, the microcable can comprise at the level of the electrodes a reinforcement of resistance to corrosion, obtained by adding a dedicated coating with very strong resistance. The corrosion resistance can also result from the choice of a structure where the noble metal of the radiopaque material forms an outer layer sheathing a core of structuring material.

A first technology used in this sense is a submicron deposition (less than 1 micron) chemically or electrochemically of a noble material, of the type mentioned above as radio-opaque materials.

Another technique consists in producing a DFT ( Drawn Filled Tube ) type composite tube with an additional layer of 1 to 2 μm of noble metal.

Yet another method consists in producing a carbon deposit of the Carbofilm (registered trademark) type which makes it possible to obtain corrosion protection and good performance in terms of hemocompatibility and biocompatibility.

If necessary, the outer surface of the insulating layer near the electrodes may contain a steroidal anti-inflammatory. In this case, a very thin steroid layer is deposited at the end of the manufacturing process by a chemical grafting or polymer crosslinking process, for example a biodegradable polymer of the PLAGA (co-glycolic polylactic acid) or PLA (polylactic acid) type. ).

It can also be envisaged that the anti-inflammatory product is contained in the material constituting the isolation layer.

Finally, the microprobe is terminated proximally by a connector intended to be connected to the generator of the implantable device.

According to a particularly advantageous aspect of the invention, because of the small size of the microprobe, it is envisaged to preform it at the electrodes to promote electrical contact with the tissues, and also to mechanically stabilize the microworld in the ships.

The preforms may be obtained by forming the metal or polymer part of the probe, for example by heat treatment.

The Figures 4a to 4d illustrate some particular embodiments of the preform: the preforms of the Figures 4a and 4b have an S-plane configuration, single or multiple, while the preforms of Figures 4c and 4d are configured as a three-dimensional spiral, single or double.

According to another aspect of the invention, a defining characteristic of a microprobe is that it can be easily manipulated by the physician during implantation.

It is also important to minimize the stiffness transitions along the probe so as to reduce the stress concentrations that can lead to fatigue embrittlement of the device. Nevertheless, a certain stiffening is necessary because an excessively flexible microprobe would limit the manipulation in thrust.

The solution to these difficulties consists of a stepped stiffening made possible by means of degression of stiffness provided between the proximal portion and the distal portion of the microprobe. It is then possible to manage the progressive stiffness gradient along the probe so as to ensure, on the one hand, a non-traumatic soft distal part allowing to pass through the tortuosities and, on the other hand, a proximal part more rigid device for transmitting the thrust exerted by the physician by means of appropriate devices.

In the example proposed at Figure 8 , the stiffness degressivity means are made by a staged stack of three tubes 51, 52, 53 nested within each other on the microcable 40. These tubes, PET (polyethylene terephthalate) for example, can have a thickness of 5 at 20 μm.

Thus, the rigidity at the proximal end of the probe can be fifty times greater than the stiffness at the distal end, without this requiring the addition of additional mechanical part. The robustness of the whole is also greatly increased.

It is also possible to envisage means of degression of rigidity realized by a succession of isodiameter tubes of decreasing rigidity, welded together. However, this technique generates risks of rupture in the welds between the tubes.

Finally, Figure 9 illustrates another variant consisting of a local enhancement of the microprobe by a succession of tubes 70 for, independently of the insulation, consolidate a preform or angulation necessary for the desired function, giving the microprobe a specific shape. We can also thermoform the end 41 of the microprobe by this type of approach.

This solid structure, without crevices, has the important advantage of being more easily sterilizable compared to conventional probes. The risks of degradation of the microprobe materials due to an overly aggressive sterilization process are thus reduced.

We will now describe particular embodiments of a microprobe according to the invention, intended to be implanted in different sites of the body.

Example 1

The Figures 10a to 10e illustrate an exemplary embodiment of a microprobe according to the invention, intended to be implanted in a vein of the coronary sinus.

The microprobe represented in Figure 10a comprises a microcable 40 whose sectional view is shown on the Figure 10b . The core cable 12 of the microcable 40 is formed from composite unitary strands 10, as can be seen in FIG. Figure 10c , a structuring metal core 1, here an MP35N alloy with a diameter of 33 μm, and an outer envelope 5 μm thick Pt / Ir 90/10 as radiopaque material 2. The ratio between the materials are 75% for the core and 25% for the outer shell. This simple structure offers good fatigue strength and corrosion resistance guaranteed by platinum.

A cable 12 with a core of 49 strands is necessary to obtain an apparent platinum surface of 0.011 mm ² , sufficient to ensure good visibility under X-ray radiography. The conductive core cable 12 then has a diameter of 0.30 mm, which which gives it enough flexibility for intravascular use, eg via the coronary sinus.

The cable 12 is covered with an ETFE type insulation layer 25 μm thick allowing good insulation, compatible with an in-line extrusion process, for a final external diameter of 0.35 mm in the distal part. 103 of the microprobe.

Apertures 30 forming electrodes are made by laser ablation in the distal portion 103 over an area of 0.5 mm ² , to minimize the current consumption.

Heat-shrinkable tubes 51 and 52 of PET are respectively placed in an intermediate zone 102 and in the proximal portion 101, 25 cm and 45 cm from the distal tip 41 of the probe, whose total useful length varies between 90 and 120 cm.

The complete structure of the microprobe is given to the Figure 10d on which it can be seen that the proximal portion 101 terminates in a transition zone 100 formed by a polyurethane tube 50 connected to a connector 200 of the IS-1 type whose end is provided with a terminal 201 for electrical connection to the implantable equipment generator.

A method of setting up such a probe, presented on the Figure 10e consists in placing the intermediate portion 102 in the coronary sinus and the multi-electrode distal portion 103 in the veins of the coronary network, thereby stimulating the left ventricle VG. This operation is performed using a catheter 300 laying which can be removed by cutting with a cutting tool ( slitter ), as for the establishment of conventional probes.

Example 2

A second exemplary embodiment of a microprobe intended to be implanted in a cardiac cavity, for example a straight cavity, is illustrated in FIGS. Figures 11a to 11d .

This microprobe comprises a microcable 40, a sectional view of which is shown in FIG. Figure 11a . The core cable 11 of the microcable 40 is formed of composite unitary strands 10, as can be seen in FIG. Figure 11b , a tantalum core 2 as a radiopaque material and an outer shell 2 of structuring material, here nitinol. The ratio between materials is 25% core and 75% for the envelope external. This simple structure provides external elasticity as well as good radiopacity provided by the inner core.

It should be remembered the advantage of nitinol to have a large memory shape, particularly favorable to contact in a large cavity.

A core cable 11 of nineteen strands is necessary to obtain a platinum apparent surface of 0.010 mm ² , sufficient to ensure good visibility under X-ray fluoroscopy. The conductive core cable 11 then has a diameter of 0.20 mm, which gives it sufficient flexibility for intra-cavitary use, ventricle and / or right atrium in particular.

The cable 11 is covered with a 25 μm thick FEP type insulation layer 20 which provides good insulation and is compatible with an in-line extrusion process, for a final external diameter of 0.25 mm in the distal part. of the microprobe.

In this embodiment, it is possible to use a polyimide or PEEK type reinforcing structure of very small thickness to retain the superelastic properties of nitinol. In this case it will be applied to the entire microcable a coating ( coating ) type Carbofilm (registered trademark) with superior resistance to corrosion, and increased biocompatibility. This type of coating, less than 1 micron, makes it possible not to modify the electrical properties of the electrode while substantially improving the surface compatibility properties with the blood.

In addition, by appropriate treatment, it is possible to give the probe a configuration that allows it to conform to the heart chamber according to the associated stimulation and anatomy needs. The Figures 11c and 11d show two possible conformations of the probe for stimulation of the right cavities.

Example 3

A third embodiment of a microprobe intended to be implanted in the cerebral cavities is illustrated on the Figures 12a to 12c .

In this example, very good radiopacity is required, as well as great flexibility and a very small diameter. On the other hand, for this type of product, MRI compatibility is fundamental.

The microcable 40 shown on the Figure 12a comprises a core cable 13 formed of composite unitary strands 10 made up, as can be seen in FIG. Figure 12b a tri-layered wire comprising (i) a core 2 of a radio-opaque material, in this case tantalum, (ii) an intermediate layer 1 made of titanium as a structuring material, and (iii) an outer palladium envelope 3 to minimize skin effects and achieve better structural compatibility with MRI. The ratio of the three materials is 30% Ta / 65% Ti / 5% Pd. This structure, although less resistant to fatigue at the strand 10, is compensated by a unit diameter of 16 microns, less mechanically constrained.

A 133-core core cable 13 (7x19) is necessary to obtain a platinum apparent surface of 0.010 mm ² , sufficient to ensure good visibility under X-ray radiography. The conductive core cable 13 then has a diameter of 0.25 mm. , very flexible for intracerebral use.

The cable 13 is covered with a mechanically more flexible FEP-type insulation layer 20 of thickness 25 μm allowing good insulation and compatible with an in-line extrusion process, for a final external diameter of 0.30. mm in the distal part of the microprobe.

A polyether block amide Pebax ( Trade Mark) may be associated with the isolation layer 20 to manage the stiffness gradients to the proximal portion of the microprobe.

An example of implantation of this probe is shown on the Figure 12c .

Claims (20)

A detection / stimulation probe intended to be implanted in venous, arterial or lymphatic networks, comprising a microcable (40) of diameter at most equal to 2 French (0.66 mm), this microcable comprising: an electrically conductive core cable (11, 12, 13, 14) of diameter at most equal to 0.50 mm, formed by a strand of a plurality of strands (10) of unit diameter (d) at most equal to 40 μm,
said core cable comprising a structuring material (1) having a high fatigue resistance; and an insulation layer (20) of polymer partially surrounding the core cable to a thickness at most equal to 30% of the diameter of the core cable, characterized in that this probe is a microprobe constituted in its active part, distal, by said microcable (40) of diameter at most equal to 2 French (0.66 mm), and in that : the core cable (11, 12, 13, 14) of the microcable has a composite structure formed from, at least, said structuring material (1) and a radiopaque material (2) constituting at least about 0.008 mm ² of the section of the heart cable in a proportion not greater than 50%, and - at least one stripped zone (30) is formed in the insulation layer (20) so as to form at least one electrode on a cumulative total surface at most equal to 20 mm ² ; and - Rigidity degressivity means (51, 52, 53) are formed along the microprobe between its proximal portion and its distal portion. The microprobe of claim 1, wherein the microprobe is shaped at the level of the electrodes (30) according to at least one preform (61, 62, 63, 64) of electrical contact and mechanical stabilization The microprobe of claim 1, wherein the unit diameter ( d ) of the strands (10) is between 20 and 40 μm. The microprobe of claim 1, wherein said structuring material (1) of the core cable comprises a stainless steel, a cobalt alloy, a precious metal, titanium or a NiTi alloy. The microprobe of claim 1, wherein the radio-opaque material (2) is a material of the group consisting of: tantalum (Ta), tungsten (W), iridium (Ir), platinum (Pt), gold (Au) and their alloys. The microprobe of claim 1, wherein the composite structure of the core cable (11, 12, 13) is formed by composite strands (10) consisting, at least, of a structuring material (1) and a material radiopaque (2). The microprobe of claim 1, wherein the composite structure of the core cable (14) is formed by strands (10 ₁ ) made of structuring material (1) and strands (10 ₂ ) made of radiopaque material (2). ). The microprobe of claim 1, wherein said plurality of strand strands comprise between 15 and 300 strands. The microprobe of claim 1 wherein the polymer constituting the isolation layer (20) is a fluoropolymer. The microprobe of claim 1, wherein the strands (10) comprise an outer layer of material (3) with low magnetic susceptibility, less than 2000.10 ^-2 m ³ .mole ^-1 . The microprobe of claim 10, wherein the low magnetic susceptibility material (3) is a material of the group consisting of: tantalum (Ta), titanium (Ti), rhodium (Rh), molybdenum (Mo), tungsten (W), palladium (Pd), gold (Au) and their alloys. The microprobe of claim 1, wherein the surface of an electrode (30) is at most 0.5 mm ² . The microprobe of claim 1, wherein the microcable (40) has at the electrodes (30) a corrosion resistance coating. The microprobe of claim 1, wherein the outer surface of the isolation layer (20) near the electrodes (30) contains an anti-inflammatory. The microprobe of claim 1, wherein the material constituting the isolation layer (20) contains an anti-inflammatory. The microprobe of claim 1, wherein the preform is a flat preform (61, 62) in S. The microprobe of claim 1, wherein the preform is a three-dimensional (63, 64) spiral preform. The microprobe of claim 1 comprising local enhancement means (70). The microprobe of claim 1, wherein the stiffness degressivity means is provided by a stack of tubes (51, 52, 53) nested within each other. The microprobe of claim 1, wherein the means of decreasing rigidity are made by a succession of isodiameter tubes of decreasing rigidity.

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